Registration Dossier

Administrative data

Endpoint:
short-term repeated dose toxicity: dermal
Type of information:
experimental study
Adequacy of study:
key study
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: purity of test substance not stated, individual quantitative results not reported. Also assessed by OECD.

Data source

Referenceopen allclose all

Reference Type:
study report
Title:
Unnamed
Year:
1979
Report Date:
1979
Reference Type:
secondary source
Title:
Triphenyl phosphate, CAS No: 115-86-6; Screening Information Dataset (SIDS) Initial Assessment Report for SIAM 15, 2002
Author:
OECD SIDS
Year:
2002
Bibliographic source:
UNEP Publications, Organisation for Economic Co-operation and Development (OECD)
Report Date:
2002

Materials and methods

Test guideline
Qualifier:
equivalent or similar to
Guideline:
EPA OPPTS 870.3200 (Repeated Dose Dermal Toxicity -21/28 Days)
GLP compliance:
not specified

Test material

Reference
Name:
Unnamed
Type:
Constituent
Specific details on test material used for the study:
description: coarse white solid

Test animals

Species:
rabbit
Strain:
New Zealand White
Sex:
male/female
Details on test animals and environmental conditions:
supplier: Marland Breeding FArms, inc. Hewitt, New Jersey 07421
weight at initiation of treatment: males mean 2.41 kg, females mean 2.42 kg
acclimation period: 24 days
food and water: ad libitum
environmental conditions: 12h light/dark cycle

Administration / exposure

Type of coverage:
other: no dressing used after application of test substance but collars were used to prevent ingestion of the material
Vehicle:
ethanol
Details on exposure:
Route of Administration: dermal exposure for 6h/day, 5 days/week over 21 to 23 days
Analytical verification of doses or concentrations:
yes
Details on analytical verification of doses or concentrations:
10 g samples of the test material were taken one week pretest and on the last day of the study and sent to the sponsor for analytical confirmation of the test material
Duration of treatment / exposure:
21-23 days
Frequency of treatment:
5 days/week
Doses / concentrations
Remarks:
Doses / Concentrations:
100 and 1000 mg/kg bw/day
Basis:
nominal per unit body weight
No. of animals per sex per dose:
10 males and 10 females per dose; the skin of the first 5 rabbits of each sex in each group was abraded twice weekly
Control animals:
yes, concurrent vehicle
Details on study design:
Post-exposure period: no
Two days prior to application of the test material an area equal to approximately 25% of the total body surface area was carefully and closely clipped on the dorsal surface. All rabbits were reclipped twice weekly.
The skin of the first 5 rabbits of each sex in each group was abraded twice weekly by producing shallow incisions, not sufficiently deep to cause bleeding but penetrating the horny layer of the epidermis.

Examinations

Statistics:
yes: body weight, hematology and clinical chemistry parameters, organ weights and oran/body weight ratios were analysed.

Results and discussion

Results of examinations

Clinical signs:
no effects observed
Dermal irritation:
no effects observed
Mortality:
no mortality observed
Body weight and weight changes:
no effects observed
Food consumption and compound intake (if feeding study):
no effects observed
Food efficiency:
no effects observed
Water consumption and compound intake (if drinking water study):
no effects observed
Ophthalmological findings:
no effects observed
Haematological findings:
no effects observed
Clinical biochemistry findings:
effects observed, treatment-related
Urinalysis findings:
no effects observed
Behaviour (functional findings):
not examined
Organ weight findings including organ / body weight ratios:
no effects observed
Gross pathological findings:
no effects observed
Details on results:
The only treatment related effect was a depression of acetyl cholinesterase in plasma, erythrocytes and brain.

Effect levels

Dose descriptor:
NOAEL
Effect level:
1 000 mg/kg bw/day
Sex:
male/female
Basis for effect level:
other: highest dose tested

Target system / organ toxicity

Critical effects observed:
not specified

Any other information on results incl. tables

CLIN.CHEMISTRY: decrease of acetylcholinesterase activity in plasma,  erythrocytes and brain in males and females
ALL OTHER PARAMETERS: comparable to control/ no effects
2 rabbits of the control group (one male, one female) died spontaneously during the course of the study.

Applicant's summary and conclusion

Conclusions:
The findings detected at the site of treatment as well as other parameters (mortality, clinical symptoms, body weight, heamatology, clinical chemistry, necropsy, organ weights, histopathology of >30 tissues (including reproductive organs and nervous system) were not different to controls. The only treatment related effect seen was a depression of acetyl cholinesterase in plasma, erthrocytes and brain of TPP treated rabbits. No clinical or histological correlations was found. No quantitative data was reported for this endpoint. This effect was not considered as of toxicological relevance.
Executive summary:

'The toxicity of TPP after repeated dermal exposure was determined in rabbits. Ten male and 10 female animals per group were treated on clipped, intact (half of the animals) and abraded skin (half of the animals), 6 hours/day, five times/week for three weeks with doses of 0, 100 and 1000 mg/kg bw/day under open conditions. Ingestion was prevented by means of a collar. TPP was applied as a 50% (w/v) solution in ethanol. The application volume was 0.2 mL or 2 mL/kg bw/day. Control animals were treated with 2 mL/kg bw/day ethanol alone. The findings detected at the site of treatment as well as other parameters (mortality, clinical symptoms, body weight, heamatology, clinical chemistry, necropsy, organ weights, histopathology of >30 tissues (including reproductive organs and nervous system)) were not different to controls. The only treatment related effect seen was a depression of acetyl cholinesterase in plasma, erthrocytes and brain of TPP treated rabbits. No clinical or histological correlations was found. No quantitative data was reported for this endpoint. This effect was not considered as of toxicological relevance.' (OECD SIDS, 2002)